Vpliv raznolikosti tkivnih antigenov HLA-C na izbiro nesorodnega darovalca pri presaditvi krvotvornih matičnih celic

diplomsko delo

Irena Kemperle (Author), Uroš Potočnik (Mentor), Blanka Vidan-Jeras (Co-mentor)

Abstract

Presajanje krvotvornih matičnih celic (KMC) se je v zadnjih desetletjih uveljavilo kot najuspešnejši način zdravljenja poprej večinoma neozdravljivih bolezni krvotvornih organov predvsem različnih vrst levkemij. Kadar bolniku ne najdemo glede na HLA enakega sorodnega darovalca, iščemo nesorodnega v registrih darovalcev krvotvornih matičnih celic. V strokovni literaturi najdemo dokaze, da neujemanja v tkivnih antigenih HLA-A, HLA-B, HLA-C in HLA-DR med darovalcem in prejemnikom KMC odločilno vplivajo na uspešnost presaditve oz. na preživetje bolnika po njej. Lokus HLA-C so med produkti genov HLA I. razreda odkrili najpozneje, tako da je njihov vpliv na izhod presaditve KMC manj raziskan. Ugotovili smo, da so za tipizacijo HLA-C najprimernejše metode, ki temeljijo na analizi DNK. Ker z eno metodo ne moremo razrešiti vseh dvoumnosti tipizacij, je trenutno po našem mnenju najboljša izbira kombinacija metod PCR-SBT in PCR- SSP. Antigene oz. alele HLA-C smo na vzorcu oseb slovenske narodnosti v različnih časovnih obdobjih tipizirali z metodama: PCR-SSO in PCR-SBT. PCR-SSP smo v obeh primerih uporabili le kot dodatno metodo. Za razliko od izbranih evropskih populacij, kjer je najpogostejši alel Cw*0701, je presenetljivo najpogostejši alel v slovenski populaciji Cw*0401. V primeru rekombinacij v antigenih HLA bolnik v družini nima primernega darovalca, prav tako je težka izbira oz. iskanje nesorodnega darovalca. Z namenom, da bi ugotovili pogostnost rekombinacij pri naših bolnikih smo analizirali 557 družin. Po določitvi haplotipov smo pri 2,7% družin opazili rekombinacijo. Ugotovili smo, da se pojavi v 40% primerov med lokusoma HLA-A in C, med lokusoma HLA-B in DRB1 pa v 60% primerov. Iz tega sklepamo, da neujemanja v HLA-C največ prispevajo k tkivni neskladnosti na lokusih HLA I. razreda. Razvidno je celo da ne gre za neujemanje v alelih HLA-C, pač pa za neujemanja v antigenih, kar predstavlja večjo oviro za presaditev KMC. Razlog je verjetno iskati v močnem vezavnem neravnovesju med lokusoma HLA-B in HLA-C, kar je razvidno tudi iz naše analize rekombinacij, ki jih med omenjenima lokusoma nismo opazili. Izsledki nekaterih študij kažejo na to, da obstaja veliko število različnih kombinacij antigenov HLA-B in HLA-C v vezavnem neravnovesju. Tako velikokrat pri darovalcu naletimo na drugačno kombinacijo antigenov HLA-B in HLA-C kot jo ima bolnik. Menimo, da bi hkratni izbor več darovalcev ter vključitev lokusa HLA-C k osnovni tipizaciji tako darovalca kot bolnika pripomogla k učinkovitejšemu in hitrejšemu zaključku preizkušanja tkivne skladnosti.

Keywords

presajanje krvotvornih matičnih celic;polimorfizem;antigeni;

Data

Language:	Slovenian
Year of publishing:	2009
Source:	Maribor
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[I. Kemperle]
UDC:	575.113:612.118(043.2)
COBISS:	13904150
Views:	2626
Downloads:	166
Average score:	0 (0 votes)
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Other data

Secondary language:	English
Secondary title:	The influence of hla-c polymorphism on matching in unrelated donor stem cell transplantation
Secondary abstract:	During the past decades transplantation of haemapoietic stem cells has proven to be the most successful treatment method of diseases of haematopoietic organs such as different types of leukaemia, previously considered as mostly incurable. In case of unavailability of genotipicaly identical related donor, a search for an unrelated donor is initiated through bone marrow donor registries. Literature offers evidence on disparities at HLA-A, HLA-B, HLA-C and HLA-DR antigens between donor and recipient of haemapoietic stem cells, playing the most important role in outcome of allogenic stem cell transplantation and survival afterwards. HLA-C locus has been the last of HLA class I loci to be discovered, therefore the impact of its products on transplantation outcome has not been studied as extensively as others. DNA based analysis have shown to be the most adequate techniques. Using one technique only, many times gives ambiguous result. The best results are, in our opinion, achieved using the combination of both PCR-SBT and PCR-SSP typing technique. In our study blood samples, obtained from individuals of Slovene nationality, were typed at two different times using PCR-SSO and PCR-SBT technique. In both cases PCR-SSP was performed as an additional technique. The study yielded surprising results. The most common allele in Slovenian population is Cw0401 as opposed to selected European populations with the highest frequency of Cw0701 allele. Recombination between HLA genes in patient significantly reduces a possibility of finding a matched unrelated donor, whereas the possibility of finding the donor among relatives is excluded. In order to determine the frequency of recombinations among Slovenian patients 557 families were analysed. Determination of haplotypes showed 2,7% frequency of recombinations among families. While in 40% of the cases, recombination occured between HLA-A and HLA-C loci, in 60% of the case the recombination occured between HLA-B and HLA-DR loci. The study showed that out of HLA I loci disparities at HLA-C locus contribute the most to incompatibility. Disparities at HLA-C have not been observed at an allele level, but always at an antigen level representing significant obstacle regarding stem cell transplantation, which probably stems from linkage disequilibrium between HLA-B and HLA-C loci, that our study supports as no recombination between these two loci was detected. Due to many different possible combinations of HLA-B and HLA-C antigens, the same combination is rarely found in both the patient and the donor. It is of our opinion that the simultaneous typing of several potential donors and a mandatory inclusion of HLA-C locus in basic typing of both the patient and the donor contribute to more efficient and faster completion of the search
Secondary keywords:	HLA-C;hemotopoetic stem cell transplantation;antigens;PCR-SSO;PCR-SSP;PCR-SBT;
URN:	URN:SI:UM:
Type (COBISS):	Undergraduate thesis
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	58 f.
Keywords (UDC):	mathematics;natural sciences;naravoslovne vede;matematika;biological sciences in general;biologija;general genetics;general cytogenetics;splošna genetika;splošna citogenetika;applied sciences;medicine;technology;uporabne znanosti;medicina;tehnika;medical sciences;medicina;physiology;human and comparative physiology;fiziologija;fiziologija človeka in primerjalna fiziologija;blood;cardiovascular;circulatory system;kri;obtočila;
ID:	987942